Although it is clear that mutations of the mitochondrial genome are more prevalent in aged mammals, the relationship between mitochondrial mutation and the pathogenesis of aging is poorly understood. In neuronal cells, mitochondrial dysfunction, apoptosis and necrosis can all be traced to mitochondrial calcium accumulation in response to a variety of toxicants. This calcium accumulation initially promotes energy metabolism but may ultimately impair ATP production and accelerate ROS production. The release of mitochondrial proteins (e.g., cytochrome c, AIF) can readily trigger apoptosis through caspase dependent and independent pathways. The mechanism by which these proteins are released from the intermembrane space remains an exciting and controversial aspect of cellular biology. Defining these mechanisms and their regulation will be critical in understanding the pathogenesis of both acute and chronic neurodegenerative diseases. The Center for Aging and Developmental Biology at the University of Rochester has initiated an annual summer school program for 15-20 neuroscientists (senior graduate students, postdoctoral fellows, and perhaps junior faculty). Students will be selected on a competitive basis in the second half of 2003. There would be 10-15 invited faculty members and several from the University of Rochester that will serve as instructors. The University has recently invested heavily in mitochondrial research: hiring new faculty, supporting a colloquium series, and creating a graduate course in mitochondrial biology. Along this vein, the theme for the inaugural program in 2004 will be Mitochondrial Disease and Aging. It will be held August 6 -10, 2004. These dates were chosen to minimize conflicts with other scheduled meetings and to take advantage of dormitory housing; the housing arrangement mirrors similar small conferences and will facilitate social and scientific interactions between students and faculty.